CA3079188A1 - Antagonists of the muscarinic acetylcholine receptor m4 - Google Patents

Antagonists of the muscarinic acetylcholine receptor m4 Download PDF

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Publication number: CA3079188A1
Authority: CA; Canada
Prior art keywords: azaspiro; pyridazin; dimethylpyrazol; nonane; compound
Prior art date: 2017-10-17
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA3079188A

Other languages

English (en)

French (fr)

Inventor

Craig W. Lindsley

P. Jeffrey Conn

Darren W. Engers

Aaron M. Bender

Julie L. Engers

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Vanderbilt University

Original Assignee

Vanderbilt University

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2017-10-17

Filing date

2018-10-17

Publication date

2019-04-25

2018-10-17 Application filed by Vanderbilt University filed Critical Vanderbilt University

2019-04-25 Publication of CA3079188A1 publication Critical patent/CA3079188A1/en

Status Abandoned legal-status Critical Current

Links

239000005557 antagonist Substances 0.000 title abstract description 21
102000000413 Muscarinic acetylcholine receptor M4 Human genes 0.000 title abstract 2
108050008897 Muscarinic acetylcholine receptor M4 Proteins 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 317
238000000034 method Methods 0.000 claims abstract description 89
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 45
-1 -NHCOR f Chemical group 0.000 claims description 110
150000003839 salts Chemical class 0.000 claims description 91
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
239000001257 hydrogen Substances 0.000 claims description 58
229910052739 hydrogen Inorganic materials 0.000 claims description 58
125000003118 aryl group Chemical group 0.000 claims description 48
125000000753 cycloalkyl group Chemical group 0.000 claims description 47
NVHXMNNCHAFIHX-UHFFFAOYSA-N pyridazin-3-amine Chemical compound NC1=CC=C=N[N]1 NVHXMNNCHAFIHX-UHFFFAOYSA-N 0.000 claims description 47
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
125000000623 heterocyclic group Chemical group 0.000 claims description 41
125000001072 heteroaryl group Chemical group 0.000 claims description 40
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
125000005843 halogen group Chemical group 0.000 claims description 39
125000001424 substituent group Chemical group 0.000 claims description 39
125000005842 heteroatom Chemical group 0.000 claims description 37
208000035475 disorder Diseases 0.000 claims description 35
239000003814 drug Substances 0.000 claims description 31
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
238000011282 treatment Methods 0.000 claims description 29
208000024891 symptom Diseases 0.000 claims description 22
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
241000124008 Mammalia Species 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
230000008485 antagonism Effects 0.000 claims description 16
208000018737 Parkinson disease Diseases 0.000 claims description 15
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 14
208000016285 Movement disease Diseases 0.000 claims description 14
230000008901 benefit Effects 0.000 claims description 14
229910052717 sulfur Inorganic materials 0.000 claims description 14
201000000980 schizophrenia Diseases 0.000 claims description 13
208000014094 Dystonic disease Diseases 0.000 claims description 11
208000010118 dystonia Diseases 0.000 claims description 11
125000005549 heteroarylene group Chemical group 0.000 claims description 11
208000015122 neurodegenerative disease Diseases 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
208000014644 Brain disease Diseases 0.000 claims description 9
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
208000012661 Dyskinesia Diseases 0.000 claims description 8
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 7
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 7
208000007590 Disorders of Excessive Somnolence Diseases 0.000 claims description 7
206010041349 Somnolence Diseases 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
206010008748 Chorea Diseases 0.000 claims description 6
208000023105 Huntington disease Diseases 0.000 claims description 6
206010034010 Parkinsonism Diseases 0.000 claims description 6
230000003042 antagnostic effect Effects 0.000 claims description 6
208000012601 choreatic disease Diseases 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
208000000323 Tourette Syndrome Diseases 0.000 claims description 5
208000016620 Tourette disease Diseases 0.000 claims description 5
125000000732 arylene group Chemical group 0.000 claims description 5
206010008129 cerebral palsy Diseases 0.000 claims description 5
230000007278 cognition impairment Effects 0.000 claims description 5
201000002212 progressive supranuclear palsy Diseases 0.000 claims description 5
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
FNQVRPKJUDYUDZ-UHFFFAOYSA-N 7-(cyclohexylmethyl)-2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-azaspiro[3.5]nonane Chemical compound C1(CCCCC1)CN1CCC2(CC(C2)OC=2N=NC(=CC=2)C=2C(=NN(C=2)C)C)CC1 FNQVRPKJUDYUDZ-UHFFFAOYSA-N 0.000 claims description 2
229910052720 vanadium Inorganic materials 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 6
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
MBDNHLUTVAEOLJ-UHFFFAOYSA-N 2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-(2,3,3-trimethylbutyl)-7-azaspiro[3.5]nonane Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC(C(C)(C)C)C)C MBDNHLUTVAEOLJ-UHFFFAOYSA-N 0.000 claims 1
JRUVIEYJZKGCIB-UHFFFAOYSA-N 2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-(oxan-3-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1COCCC1)C JRUVIEYJZKGCIB-UHFFFAOYSA-N 0.000 claims 1
NHIGASHGHRLYLM-UHFFFAOYSA-N 2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-(oxan-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1CCOCC1)C NHIGASHGHRLYLM-UHFFFAOYSA-N 0.000 claims 1
JFIPHOWIAHNGHB-UHFFFAOYSA-N 2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-(thian-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1CCSCC1)C JFIPHOWIAHNGHB-UHFFFAOYSA-N 0.000 claims 1
CUDQJVLSUNNSPK-UHFFFAOYSA-N 2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-[(3-methylpyridin-2-yl)methyl]-7-azaspiro[3.5]nonane Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1=NC=CC=C1C)C CUDQJVLSUNNSPK-UHFFFAOYSA-N 0.000 claims 1
LPNPNWKZCXIMML-UHFFFAOYSA-N 2-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]oxy-7-(2,3,3-trimethylbutyl)-7-azaspiro[3.5]nonane Chemical compound CC(CN1CCC2(CC(C2)Oc2ccc(nn2)-c2c(C)cnn2C)CC1)C(C)(C)C LPNPNWKZCXIMML-UHFFFAOYSA-N 0.000 claims 1
CMFOEGWZZGOXMV-UHFFFAOYSA-N 2-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]oxy-7-(oxan-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound CN1N=CC(=C1C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1CCOCC1)C CMFOEGWZZGOXMV-UHFFFAOYSA-N 0.000 claims 1
MINSIMNPVPNEKL-UHFFFAOYSA-N 2-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]oxy-7-(thian-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound CN1N=CC(=C1C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1CCSCC1)C MINSIMNPVPNEKL-UHFFFAOYSA-N 0.000 claims 1
DTRCFVAZPVPAMM-UHFFFAOYSA-N 2-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]oxy-7-[(3-methylpyridin-2-yl)methyl]-7-azaspiro[3.5]nonane Chemical compound CN1N=CC(=C1C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1=NC=CC=C1C)C DTRCFVAZPVPAMM-UHFFFAOYSA-N 0.000 claims 1
UEYLUEVMSRXBCT-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-(2,3,3-trimethylbutyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC(C(C)(C)C)C UEYLUEVMSRXBCT-UHFFFAOYSA-N 0.000 claims 1
OCFNRADBYJXUSZ-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-(3,3-dimethylbutyl)-7-azaspiro[3.5]nonane Chemical compound CC(C)(C)CCN1CCC2(CC(C2)Oc2ccc(nn2)-c2cc(F)ccc2Cl)CC1 OCFNRADBYJXUSZ-UHFFFAOYSA-N 0.000 claims 1
XYNZTVQAWYPIKZ-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-(cyclohexylmethyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1CCCCC1 XYNZTVQAWYPIKZ-UHFFFAOYSA-N 0.000 claims 1
JACJQKJWLMAMMG-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-(oxan-3-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1COCCC1 JACJQKJWLMAMMG-UHFFFAOYSA-N 0.000 claims 1
ICFFPZBBPIWRGQ-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-(oxan-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1CCOCC1 ICFFPZBBPIWRGQ-UHFFFAOYSA-N 0.000 claims 1
NTIZOACULRTICN-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-(thian-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound Fc1ccc(Cl)c(c1)-c1ccc(OC2CC3(C2)CCN(CC2CCSCC2)CC3)nn1 NTIZOACULRTICN-UHFFFAOYSA-N 0.000 claims 1
XZFBLNQTBHVSND-UHFFFAOYSA-N 2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-[(3-methylpyridin-2-yl)methyl]-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OC1CC2(C1)CCN(CC2)CC1=NC=CC=C1C XZFBLNQTBHVSND-UHFFFAOYSA-N 0.000 claims 1
IJKRKMSULKEGHT-UHFFFAOYSA-N 2-[[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxymethyl]-7-(3,3-dimethylbutyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OCC1CC2(C1)CCN(CC2)CCC(C)(C)C IJKRKMSULKEGHT-UHFFFAOYSA-N 0.000 claims 1
DYXFSDCNFKTQQD-UHFFFAOYSA-N 2-[[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxymethyl]-7-(oxan-3-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OCC1CC2(C1)CCN(CC2)CC1COCCC1 DYXFSDCNFKTQQD-UHFFFAOYSA-N 0.000 claims 1
VVZQZAAHUYRZHS-UHFFFAOYSA-N 2-[[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxymethyl]-7-(oxan-4-ylmethyl)-7-azaspiro[3.5]nonane Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)OCC1CC2(C1)CCN(CC2)CC1CCOCC1 VVZQZAAHUYRZHS-UHFFFAOYSA-N 0.000 claims 1
SJQRCXMVCSPPEA-UHFFFAOYSA-N 6-(1,3-dimethylpyrazol-4-yl)-N-[[7-(oxan-3-ylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1COCCC1)C SJQRCXMVCSPPEA-UHFFFAOYSA-N 0.000 claims 1
GFCFZVGBWQZOAN-UHFFFAOYSA-N 6-(1,3-dimethylpyrazol-4-yl)-N-[[7-(oxan-4-ylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1CCOCC1)C GFCFZVGBWQZOAN-UHFFFAOYSA-N 0.000 claims 1
WXXKJBQYPHPJGP-UHFFFAOYSA-N 6-(1,3-dimethylpyrazol-4-yl)-N-[[7-(pyridin-2-ylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1=NC=CC=C1)C WXXKJBQYPHPJGP-UHFFFAOYSA-N 0.000 claims 1
BTXBDVZXLCRTPG-UHFFFAOYSA-N 6-(1,3-dimethylpyrazol-4-yl)-N-[[7-[(2-fluorophenyl)methyl]-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1=C(C=CC=C1)F)C BTXBDVZXLCRTPG-UHFFFAOYSA-N 0.000 claims 1
IWAKDWBPIYVUEG-UHFFFAOYSA-N 6-(1,3-dimethylpyrazol-4-yl)-N-[[7-[(3-methylpyridin-2-yl)methyl]-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1=NC=CC=C1C)C IWAKDWBPIYVUEG-UHFFFAOYSA-N 0.000 claims 1
KHBWORMHIDQRAQ-UHFFFAOYSA-N 6-(1,3-dimethylpyrazol-4-yl)-N-[[7-[(4-fluorophenyl)methyl]-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound CN1N=C(C(=C1)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1=CC=C(C=C1)F)C KHBWORMHIDQRAQ-UHFFFAOYSA-N 0.000 claims 1
BWYOWOMEMDLUOL-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-(3,3-dimethylbutyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CCC(C)(C)C BWYOWOMEMDLUOL-UHFFFAOYSA-N 0.000 claims 1
MKHINOYZCKMCBJ-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-(cyclohexylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1CCCCC1 MKHINOYZCKMCBJ-UHFFFAOYSA-N 0.000 claims 1
HNTWZVNWUCTTIT-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-(oxan-3-ylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1COCCC1 HNTWZVNWUCTTIT-UHFFFAOYSA-N 0.000 claims 1
MKHOTMVHFYJIAH-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-(oxan-4-ylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound FC1=CC(=C(Cl)C=C1)C1=CC=C(NCC2CC3(C2)CCN(CC2CCOCC2)CC3)N=N1 MKHOTMVHFYJIAH-UHFFFAOYSA-N 0.000 claims 1
HVXSWDCGJOYHDX-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-(pyridin-2-ylmethyl)-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1=NC=CC=C1 HVXSWDCGJOYHDX-UHFFFAOYSA-N 0.000 claims 1
SURDIRPTIBTUFE-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-[(2-fluorophenyl)methyl]-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NCC1CC2(C1)CCN(CC2)CC1=C(C=CC=C1)F SURDIRPTIBTUFE-UHFFFAOYSA-N 0.000 claims 1
IFTIEHAFRPKBNO-UHFFFAOYSA-N 6-(2-chloro-5-fluorophenyl)-N-[[7-[(6-methoxypyridin-2-yl)methyl]-7-azaspiro[3.5]nonan-2-yl]methyl]pyridazin-3-amine Chemical compound COc1cccc(CN2CCC3(CC(CNc4ccc(nn4)-c4cc(F)ccc4Cl)C3)CC2)n1 IFTIEHAFRPKBNO-UHFFFAOYSA-N 0.000 claims 1
SIGBKEATEUQYJP-UHFFFAOYSA-N 7-(2-bicyclo[2.2.1]hept-5-enylmethyl)-2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-azaspiro[3.5]nonane Chemical compound Cc1nn(C)cc1-c1ccc(OC2CC3(C2)CCN(CC2CC4CC2C=C4)CC3)nn1 SIGBKEATEUQYJP-UHFFFAOYSA-N 0.000 claims 1
JZVRFMJVYGXIJD-UHFFFAOYSA-N 7-(2-bicyclo[2.2.1]hept-5-enylmethyl)-2-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]oxy-7-azaspiro[3.5]nonane Chemical compound C12C=CC(C(C1)CN1CCC3(CC(C3)OC=3N=NC(=CC=3)C=3N(N=CC=3C)C)CC1)C2 JZVRFMJVYGXIJD-UHFFFAOYSA-N 0.000 claims 1
ULIXUPBOHMKFFX-UHFFFAOYSA-N 7-(2-bicyclo[2.2.1]hept-5-enylmethyl)-2-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxy-7-azaspiro[3.5]nonane Chemical compound C12C=CC(C(C1)CN1CCC3(CC(C3)OC=3N=NC(=CC=3)C3=C(C=CC(=C3)F)Cl)CC1)C2 ULIXUPBOHMKFFX-UHFFFAOYSA-N 0.000 claims 1
WTUUKCYALSCPHP-UHFFFAOYSA-N 7-(2-bicyclo[2.2.1]hept-5-enylmethyl)-2-[[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]oxymethyl]-7-azaspiro[3.5]nonane Chemical compound C12C=CC(C(C1)CN1CCC3(CC(C3)COC=3N=NC(=CC=3)C3=C(C=CC(=C3)F)Cl)CC1)C2 WTUUKCYALSCPHP-UHFFFAOYSA-N 0.000 claims 1
RQPXMLQXTWCPIK-UHFFFAOYSA-N 7-(2-bicyclo[2.2.1]hept-5-enylmethyl)-N-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]-7-azaspiro[3.5]nonan-2-amine Chemical compound C12C=CC(C(C1)CN1CCC3(CC(C3)NC=3N=NC(=CC=3)C=3C(=NN(C=3)C)C)CC1)C2 RQPXMLQXTWCPIK-UHFFFAOYSA-N 0.000 claims 1
YIJCVJATOQWSRL-UHFFFAOYSA-N 7-(2-bicyclo[2.2.1]hept-5-enylmethyl)-N-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]-7-azaspiro[3.5]nonan-2-amine Chemical compound C12C=CC(C(C1)CN1CCC3(CC(C3)NC=3N=NC(=CC=3)C=3N(N=CC=3C)C)CC1)C2 YIJCVJATOQWSRL-UHFFFAOYSA-N 0.000 claims 1
ZRZCKOCSYVWJNA-UHFFFAOYSA-N 7-(3,3-dimethylbutyl)-2-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]oxy-7-azaspiro[3.5]nonane Chemical compound CC(CCN1CCC2(CC(C2)OC=2N=NC(=CC=2)C=2C(=NN(C=2)C)C)CC1)(C)C ZRZCKOCSYVWJNA-UHFFFAOYSA-N 0.000 claims 1
VZNXMTUMAPQCGZ-UHFFFAOYSA-N 7-(3,3-dimethylbutyl)-2-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]oxy-7-azaspiro[3.5]nonane Chemical compound CC(CCN1CCC2(CC(C2)OC=2N=NC(=CC=2)C=2N(N=CC=2C)C)CC1)(C)C VZNXMTUMAPQCGZ-UHFFFAOYSA-N 0.000 claims 1
DCFXREFTKLGTJB-UHFFFAOYSA-N 7-(3,3-dimethylbutyl)-N-[6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-yl]-7-azaspiro[3.5]nonan-2-amine Chemical compound CC(CCN1CCC2(CC(C2)NC=2N=NC(=CC=2)C=2C(=NN(C=2)C)C)CC1)(C)C DCFXREFTKLGTJB-UHFFFAOYSA-N 0.000 claims 1
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DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
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PHTUQLWOUWZIMZ-GZTJUZNOSA-N trans-dothiepin Chemical compound C1SC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 PHTUQLWOUWZIMZ-GZTJUZNOSA-N 0.000 description 1
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229940066528 trichloroacetate Drugs 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
239000003029 tricyclic antidepressant agent Substances 0.000 description 1
ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
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ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 1
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238000004704 ultra performance liquid chromatography Methods 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
229960000607 ziprasidone Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA3079188A 2017-10-17 2018-10-17 Antagonists of the muscarinic acetylcholine receptor m4 Abandoned CA3079188A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US201762573569P	2017-10-17	2017-10-17
US62/573,569		2017-10-17
PCT/US2018/056233 WO2019079410A1 (en)	2017-10-17	2018-10-17	ANTAGONISTS OF THE MUSCARINIC RECEPTOR OF ACETYLCHOLINE M4

Publications (1)

Publication Number	Publication Date
CA3079188A1 true CA3079188A1 (en)	2019-04-25

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ID=66174644

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA3079188A Abandoned CA3079188A1 (en)	2017-10-17	2018-10-17	Antagonists of the muscarinic acetylcholine receptor m4

Country Status (6)

Country	Link
US (1)	US11149022B2 (de)
EP (1)	EP3697781B1 (de)
JP (1)	JP2020537667A (de)
AU (1)	AU2018352828A1 (de)
CA (1)	CA3079188A1 (de)
WO (1)	WO2019079410A1 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2020526557A (ja) *	2017-07-12	2020-08-31	ヴァンダービルトユニバーシティー	ムスカリン性アセチルコリン受容体ｍ４のアンタゴニスト
KR20250037575A (ko)	2017-10-20	2025-03-17	반더빌트유니버시티	무스카린성 아세틸콜린 수용체 m4의 길항제
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2018
- 2018-10-17 US US16/756,430 patent/US11149022B2/en active Active
- 2018-10-17 AU AU2018352828A patent/AU2018352828A1/en not_active Abandoned
- 2018-10-17 JP JP2020521586A patent/JP2020537667A/ja active Pending
- 2018-10-17 WO PCT/US2018/056233 patent/WO2019079410A1/en not_active Ceased
- 2018-10-17 EP EP18867417.0A patent/EP3697781B1/de active Active
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AU2018352828A1 (en)	2020-04-23
EP3697781C0 (de)	2023-06-07
EP3697781A4 (de)	2021-06-30
EP3697781A1 (de)	2020-08-26
US11149022B2 (en)	2021-10-19
EP3697781B1 (de)	2023-06-07
WO2019079410A1 (en)	2019-04-25
JP2020537667A (ja)	2020-12-24
US20210188811A1 (en)	2021-06-24

Publication	Publication Date	Title
US11352344B2 (en)	2022-06-07	Antagonists of the muscarinic acetylcholine receptor M4
US11325896B2 (en)	2022-05-10	Antagonists of the muscarinic acetylcholine receptor M4
EP3651762B1 (de)	2024-07-03	Antagonisten des muskarinischen acetylcholinrezeptors m4
EP3746421B1 (de)	2023-11-29	Antagonisten des muskarinischen acetylcholinrezeptors m4
EP3665175B1 (de)	2022-10-05	Antagonisten des muskarinischen acetylcholinrezeptors m4
EP3697781B1 (de)	2023-06-07	Antagonisten des muskarinischen acetylcholinrezeptors m4
EP4247803A1 (de)	2023-09-27	Antagonisten des muskarinischen acetylcholinrezeptors m4
EP4196473B1 (de)	2024-10-02	Antagonisten des muskarinischen acetylcholinrezeptors m4
US12516067B2 (en)	2026-01-06	Antagonists of the muscarinic acetylcholine receptor M4

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